Preparation of certain hydroxybenzo-heterocyclic compounds



United States Patent cc 3,317,552

Patented May 2, 1967 lower alkyl (C -C group. Non-limiting examples of the 3,317,552 keto-benzoheterocyclic compound reactant are PREPARATION OF CERTAIN HYDROXYBENZO- v HETEROCYCLIC COMPOUNDS 4 keto 4,5,6,7 tetrahydrobenzothiophene,

Harold A. Kaufman, Piscataway Township, Middlesex i gw g t Z County John R. Kilsheimer, Westfield, and Harold M. eto'4r7'dlhydl'obenlot P Foster, Middlesex, N.J., assignors to Mobil Oil Corpoahy r0-7-cyanobenzothrophene;

ti co oration of New York 4-keto-2,4,5,6,7,7a-hexahydrobenzothiophene; 1 1 0 i i'a hvin g j Filed May 25, 1965, Ser. No. 458,771 4-keto-2,3,3a,4,5,6,7,7a-octahydrobenzothiophene; 3 Ciailns- 4-keto-4,5,6,7-tetrahydrobenzothiazole;

4-ke-to-4,5,6,7-tetrahydrobenzoxazole; This invention relates to the manufacture of hydroxy- 4-keto-4,5,6,7-tetfahydfohenlofllfan; benzoheterocyclic compounds, such as 4-hydroxybenzo- 7 keto Y y thiophene. It is particularly concerned with an improved fur races for the li uid hase s nthesis of them. 5-keto-5,6,7,s-tetrahydrotlninoiine; and

p B f s l th g d, 4.h d b 15 4-keto-6-methyl-4,5,6,7-tetrahydrobenzothlophene. thiophene, is an organic intermediate for the synthesis of The Sulfur madam is elemental Sulfur in any of its N-substituted benzothienylcarbamates, which have excelforms, in rhombic monoclinic or amorphous. Stoichio lent pesticidal properties. This intermediate was prep metrically, there is required at least one mole of sulfur for by reaction of 4-ket'o-4,5,6,7-tetrahyd-robenzothiophene e h mole of hydrogen (H removed. In practice, howand Sulfur by Fiesel" and Kenneny Chemsoc-r i ever, it is preferred to use a molar excess over the stoi- 161116 6 y reported the best Yiehis chiometric amount. Thus molar excesses of one mole to tained were 6 Attempts have been made to reproduce 2.5 moles are efiective. A substantial excess should be this Preparation by other Workers Kitchen and avoided, because yields are adversely affected. Sandin, J- Am- C 67, 16454645 (1945)) and The solvent employed in the process of this invention y the inventors, but the reproducibility Was P and must be capable of dissolving both the sulfur and the yields were low. This was attributable to difiiculties in 4 keto benzot.hiophene reactant i h ld or after warmcontrolling the exothermic reaction which resulted in overing and have a boiling point of between about 175 C heating and excessive tar formation and about 350 C. However, solvents boiling below about t r hYdfoXY'henZOhetemeyehe compounds, Such as 300 C. are preferred to minimize the need for expensive hydroxyhenlofutan and hydroxyqninoiine, at e Well known temperature control means. In general, utilizable solvents in t e as are their uses- They, also, can he made by are oxygen-containing, non-carbonyl-containing comdehydregenatihg the corresponding at least Partially satu' pounds, such as alcohols, glycols, ethers, and glycolethers, rated keto-benzoheterocyclic compound with sulfur. As and various aromatic hydrocarbons N li i i exam- With the aforementioned hydroxybenlethiophene ples of utilizable solvents are diamyl ether, amyl phenyl thesis, however, difiiculties of control are encountered. ether, b yl ethyl ether, butylene glycol, 2-butoxy-1 It is a discovery of this invention that the at least parethanol, butyl Pheny] ether, i l h l decanol, ditially saturated keto-benzoheterocyclic compounds can be ethylene glycol, -b l h di h l ether, d dehydfegenated With sulfur in higher yield and With decanol, ethylbenzyl alcohol, 2-ethyl-1-hexanol, glycerol Prodllcible results, When dehydrogenation is conducted 40 methyl ether, hexadecanol, di-n-heptyl ether, dioctylether, in a solvent for both the sulfur and the keto-benzoheteroi h h ether, h p l h l propanediol, m-

y i Compound Ieaetantethylene glycol, Z-phenoxy-l-ethanol, l-methyl naphthal- Accordingly, a broad object of this invention 1s to prod di h 1 h h 1 Vide an improved Process for Preparing Y y- In general, the reaction is carried out at temperatures heterocyclic compounds- Another Object is to p i an between about 175 0. and about 350 c. and, preferably, improved process for earrylng out the dehydrosenatlon-of between about 200 c. and about 275 c. The reaction a keto-benloheteroeyclio ooInPonnd feaetant- A specific time will be between about /2 hour and about 5 hours. object is to Provide an improved Process for dehydrogenat- Usually, the reaction time is between about one hour and ing a hydrogenated keto-benzoheterocyclic compound reabout 3 h actant with elemental sulfur using a solvent for both the I the following example, the process of this invention sulfur and the keto-benzoheterocyclic compound reactant. i d mo trated by the dehydrogenation of 4-keto-4 5,6,7- Another specific Object is to Provide an improved Pfeeess tetrahydrobenzothiophene to 4-hydroxybenzoth1ophene, for P p g 4hYdIOXYhenZOthiOPheneother objects using drphenyl ether, a preferred solvent. It Will be undersnd advantages of this invention Will heeotn'e pp stood that other solvents can be used and that, using this to those Skill d in t e art from the following detailed process, other keto-benzoheterocychc compound reactants description.

This invention provides a process for producing hydroxy-benzoheterocyclic compounds that comprises heating a solution of elemental sulfur and a keto-benzohetero- Example cyclic compound reactant in a solvent for both sulfur and A mixture of 22 parts 4-keto-4,5,6,7-tetrahydrobenzosaid reactant. thiophene, 9 parts sulfur, and 30 parts diphenyl ether The material that is dehydrogenated in the process of were charged to a reaction vessel provided with a stirrer this invention is an at least partially saturated keto-benzoand a distillation head. Upon heating and stirring the 4- heterocyclic compound reactant. This reactant is an orket0-4,5,6,7-tetrahydrobenzothiophene and the sulfur disganic compound having at least one ring containing six solved in the diphenyl ether. When the temperature carbon atoms, one of said carbon atoms having attached reached 212-217" C., the reaction solution commenced thereto a keto oxygen atom, and having a heterocyclic to boil. At a pot temperature of 227 0., H 8 was ring fused thereto. At least two of the carbon atoms of evolved and exotherm occurred. Reflux was adjusted to said reactant are saturated with respect to hydrogen. The a pot temperature of 245 C. and this temperature was saturated keto-heterocycle compound reactant can be maintained for one hour. Then, the contents of the remoderately substituted with lower alkyl (C -C groups, actor were distilled out at -165 C. at 4.5 mm. mernitrile groups or ester groups (COOR) where R is a cury pressure. The distillate was extracted with 10% sodium hydroxide. Upon acidifying the extract there was obtained 14.4 parts 4-hydroxybenzothiophene (M.P.:74-78 C.)

a yield of 65.5%.

In a similar manner, ketoncs such as 4-keto-4,5,6,7-tetrahydrobenzothiazole; 4-keto-4,5,6,7-tetrahydrobenzofuran; and 4-keto-4,5,6,7-tetrahydrobenzoxazole can be converted, respectively into 4-hydroxybenzothiazole, 4-hydroxybenzofuran, and 4-hydroxybenzoxazole.

Although the present invention has been described with preferred embodiments, it is to be understood that modifications and variations may be resorted to, without departing from the spirit and scope of this invention, as those skilled in the art will readily understand. Such variations and modifications are considered to be within the purview and scope of the appended claims.

What is claimed is:

1. A process for producing hydroXy-benzoheterocyclic compounds that comprises heating a solution of elemental sulfur and a keto-benzoheterocyclic compound reactant selected from the group consisting of 4-keto-4,5,6,7-tetrahydrobenzothiophene; 4-keto-2,3,4,5,6,7-hexahydrobenzothiophene; 4-keto-4,7-dihydrobenzothiophene; 4-keto-4,5, 6,7-tetrahydro-7-cyanobenzothiophene; 4-keto-2,4,5,6,7, 7a-hexahydrobenzothiophene; 4-keto-2,3,3a,4,5,6,7,7a-octahydrobenzothiophene', 4-keto-4,5,6,7-tetrahydrobenzothiazole; 4-keto-4,5,6,7-tetrahydrobenzoxazole; 4-keto-4, 5,6,7-tetrahydrobenzofuran; 7-keto-2,3-dimethyl-2,3,3a,4, 5,6,7,7a-octahydrobenzofuran; -keto-5,6,7,8-tetrahydroquinoline; and 4-keto-6-methyl-4,5,6,7-tetrahydrobenzothiophene in a solvent for both sulfur and said reactant selected from the group consisting of diamyl ether, amyl phenyl ether, benzyl ethyl ether, butylene glycol, 2-butoxy-l-ethauol, butyl phenyl ether, cuminyl alcohol, deca- 4 nol, diethylene glycol, mono-n-butyl ether, diphenyl ether, dodecanol, ethylbenzyl alcohol, Z-ethyl-l-hexanol, glycerol methyl ether, hexadecanol, di-n-heptyl ether, dioctylether, dinaphthyl ether, methyl-cyclohexanol, propanediol, triethylene glycol, and 2-phenoxy-l-ethanol.

2. The process defined in claim 1 wherein said solvent is an ether boiling between about C. and about 350 C.

3. The process defined in claim 1 wherein said solvent is diphenyl ether.

4. The process defined in claim 2 wherein said ketobenzoheterocyclic compound reactant is 4-keto-4,5,6,7- tetrahydrobenzothiophene.

5. The process defined in claim 3 wherein said ketobenzoheterocyclic compound reactant is 4-keto-4,5,6,7- tetrahydrobenzothiophene.

6. The process defined in claim 2 wherein said ketobenzoheterocyclic compound reactant is 4-keto-4,5,6,7- tetrahydrobenzothiazole.

7. The process defined in claim 2 wherein said ketobenzoheterocyclic compound reactant is 4-keto-4,5,6,7- tetrahydrobenzofuran.

8. The process defined in claim 2 wherein said ketobenzoheterocyclic compound reactant is 4-keto-4,5,6,7- tetrahydrobenzoxazole.

References Cited by the Examiner Fieser et al., J. Am. Chem. Soc., vol. 57 (1937), p. 1615.

MacArdle, Use of Solvents, 1925, pp. 1-3.

ALEX MAZEL, Primary Examiner. RICHARD J. GALLAGHER, Assistant Examiner. 

1. A PROCESS FOR PRODUCING HYDROXY-BENZOHETEROCYCLIC COMPOUNDS THAT COMPRISES HEATING A SOLUTION OF ELEMETAL SULFUR AND A KETO-BENZOHETEROCYCLIC COMPOUND REACTANT SELECTED FROMT HE GROUP CONSISTING OF 4-KETO-4,5,6,7-TETRAHYDROBENZOTHIOPHENE; 4-KETO-2,3,4,5,6,7-HEXAHYDROBENZOTHIOPHENE; 4-KETO-4,7-DIHYDROBENZOTHIOPHENE; 4-KETO-4,5, 6,7-TETRAHYDRO-7-CYANOBENZOTHIOPHENE; 4-KETO-2,4,5,6,78 7A-HEXAHYDROBENZOTHIOPENE; 5-KETO-2,3,3A,4,5,6,7,7A-OCTAHYDROBENZOTHIOPHENE; 4-KETO-4,5,6,7-TETRAHYDROBENZOTHIAZOLE; 4-KETO-4,5,6,7-TETRAHYDROBENZOXAZOLE; 4-KETO-4, 5,6,7-TETRAHYDROBENZOFURAN; 7-KETO-2,3-DIMETHYL-2,3,3A,4, 5,6,7,7A-OCTAHYDROBENZOFURAN; 5-KETO-5,6,7,8-TETRAHYDROQUINOLINE; AND 5-KETO-6-METHYL-4,5,6,M-TETRAHYDROBENZOTHIOPHENE IN A SOLVENT FOR BOTH SUFLUR AND SAID REACTANT SELECTED FROM THE GROUP CONSISTING OF DIAMYL ETHER, AMYL PHENYL ETHER, BENZYL ETHYL ETHER, BUTYLENE GLYCOL, 2-BUTOXY-1-ETHANOL, BUTYL PHENYL ETHER, CUMINYL ALCOHOL, DECATOXY-1-ETHANOL, BUTYL PHENYL ETHER, CUMINYL ALCOHOL, DECANOL, DIETHYLENE GLYCOL, MONO-N-BUTYL ETHER, DIPHENYL ETHER, DODECANOL, ETHYLBENZYL ALCOHOL, 2-ETHYL-1-HEXANOL, GLYCEROL METHYL ETHER, HEXADECANOL, DI-N-HEPTYL ETHER, DIOCTYLETHER, DINAPHTHYL ETHER, METHYL-CYCLOHEXANOL, PROPANEDIOL, TRIETHYLENE GLYCOL, AND 2-PHENOXY-1-ETHANOL. 